Despite the development of newer and more effective antibiotic therapies, sepsis related mortality in neonates undergoing intensive care has remained constant for nearly two decades. The rate of infection among these neonates ranges from 25% to 50%, with bacterial infection remaining a major cause of death and long-term morbidity. The cost of caring for premature neonates, who are the most susceptible to infection, represents over 50% of the total dollars expended for neonatal intensive care unit (NICU) services. The unique susceptibility of the human neonate to serious and overwhelming bacterial infections relates in part to deficiencies of antibody, complement, and T lymphocytes. However, while deficiencies in these contribute to the neonate s susceptibility, neutrophil defects appear to be the major host defense abnormality. Functional defects in neonatal polymorphonuclear leukocyte adherence, aggregation, chemotaxis, phagocytosis, and intracellular killing have been described in both the term and preterm infant. Of these defects, neutrophil chemotaxis, as assessed by in vitro assays, is abnormal at birth. While term infants rapidly establish normal chemotactic function, the process of postnatal maturation begins two to three weeks after birth in the preterm infant and proceeds very slowly. Neutrophils follow a concentration gradient of chemotactic factors in their movement from the vascular compartment to the site of microbial invasion. Chemokines are chemotactic cytokines that largely control leukocyte migration. While considerable information has emerged in the past ten years related to the role of chemokines in the adult, very little information exists as to the physiologic significance of chemokines in the neonate. Candidate chemokine/chemokine receptors for influencing neutrophil chemotaxis include members of the CXC chemokines. We propose that understanding the gene regulation for the expression of specific chemokine receptors (CXCR) during development would enhance our understanding of chemotaxis in the neonate. We further propose that defining circulating concentrations of chemokines critical for neutrophil migration would be essential to understanding their role in both health and disease.